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1.
Cancer Res ; 57(11): 2085-8, 1997 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-9187099

RESUMO

Inactivating mutations in the PTCH gene, a human homologue of the Drosophila segment polarity gene patched, have been identified recently in patients with nevoid basal cell carcinoma syndrome. These patients are predisposed to various neoplasias including basal cell carcinomas and medulloblastomas (MBs). To determine the involvement of PTCH in sporadic MBs, which represent the most frequent malignant brain tumors in children, we screened for PTCH alterations in an unselected panel of 64 biopsy samples from 62 patients and four continuous MB cell lines, all derived from patients with sporadic MBs. Using single-strand conformational polymorphism analysis, we screened exons 2-22 and detected nonconservative PTCH mutations in 3 of 11 samples from sporadic cases of the desmoplastic variant of MB but none in 57 MBs with classical (nondesmoplastic) histology. In two of the tumors with mutations and in two additional desmoplastic cases, loss of heterozygosity was found at 9q22. These findings suggest that PTCH represents a tumor suppressor gene involved in the development of the desmoplastic variant of MB.


Assuntos
Neoplasias Cerebelares/genética , Meduloblastoma/genética , Proteínas de Membrana/genética , Adolescente , Animais , Criança , Pré-Escolar , Feminino , Regulação Neoplásica da Expressão Gênica , Variação Genética , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mutação , Receptores Patched , Receptor Patched-1 , Polimorfismo Conformacional de Fita Simples , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Receptores de Superfície Celular , Análise de Sequência de DNA , Células Tumorais Cultivadas
2.
J Neuropathol Exp Neurol ; 54(2): 245-54, 1995 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7876892

RESUMO

Malformative glioneuronal lesions were examined in surgical specimens from 43 patients with chronic focal epilepsies in order to determine the scope of histopathological changes and to better understand their pathogenesis. The most common lesions were hamartias composed of randomly oriented neurons and astrocytes (24 cases). Most of these lesions also contained clustered oligodendrocyte-like cells which were often strongly immunoreactive for the developmentally regulated embryonal form of the neural cell adhesion molecule (E-NCAM). These hamartias were typically minute, multifocal, and arranged in a pattern suggestive of a migration disorder. There were eight cases with aggregates of large disfigured neurons, oversized atypical astrocytes and ballooned multinucleated giant cells reminiscent of tuberous sclerosis-associated changes. Finally, there were 11 dysembryoplastic neuroepithelial tumors (DNT), an entity which has been proposed to be malformative rather than neoplastic. The oligodendroglia-like cells in DNT were negative for E-NCAM. However, strong E-NCAM expression was present in many dysplastic neurons of tuberous sclerosis-like lesions, hamartias and DNT and in reactive astrocytes. Significant immunoreactivity for the proliferation associated Ki-67 antigen was not observed. No similar lesions were observed in 500 consecutive autopsies from patients without epilepsy. Malformative glioneuronal lesions appear to be highly epileptogenic and most likely result from a disordered cell migration and differentiation.


Assuntos
Encéfalo/anormalidades , Epilepsias Parciais/patologia , Neuroglia/patologia , Autopsia , Moléculas de Adesão Celular Neuronais/análise , Doença Crônica , Resistência a Medicamentos , Epilepsias Parciais/tratamento farmacológico , Epilepsias Parciais/cirurgia , Humanos , Imuno-Histoquímica , Neoplasias Neuroepiteliomatosas/patologia , Esclerose Tuberosa/patologia
3.
J Neuropathol Exp Neurol ; 54(5): 689-97, 1995 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-7666058

RESUMO

Gangliogliomas, dysembryoplastic neuroepithelial tumors (DNT) and glioneuronal malformations are frequently encountered in patients with pharmacoresistant focal epilepsies. In order to characterize the neurochemical profile of these neoplastic and malformative glioneuronal lesions, we have examined the presence of the alpha 1 subunit of the GABAA receptor, the N-methyl-D-aspartate receptor subunit 1 (NR1), glutamate decarboxylase, tyrosine hydroxylase, somatostatin, parvalbumin, and calretinin in 60 gangliogliomas, 11 DNT, 10 tuberous sclerosis-like lesions and 17 non-tuberous sclerosis-like glioneuronal malformations. All DNT and tuberous sclerosis-like lesions, 59 gangliogliomas (98%), and 13 non-tuberous sclerosis-like hamartias (76%) were positive for at least one of the markers. Despite a great variation between and within the different entities, the neurochemical profile was generally reminiscent of normal neocortex: glutamate decarboxylase, GABAA receptor and NR1 which are common in neocortical neurons were present in the great majority of the lesions and often showed high labeling indices. There were three tuberous sclerosis-like lesions (30%) that contained both NR1 and glutamate decarboxylase immunoreactive giant cells in addition to well-differentiated ganglion cells. This supports the idea that at least some of these giant cells are of neuronal origin. The oligodendroglia-like cells of DNT and glioneuronal hamartias did not show immunoreactivity for any of the markers. The very high incidence of ganglioglial lesions in patients with chronic focal epilepsies and the presence of neurotransmitter-producing enzymes, neurotransmitter receptors, neuropeptides, and calcium-binding proteins in many of these lesions suggests that they may play an active role in the pathogenesis of epileptic seizures.


Assuntos
Neoplasias Encefálicas/patologia , Epilepsias Parciais/patologia , Ganglioglioma/patologia , Proteínas do Tecido Nervoso/análise , Neuroglia/patologia , Neurônios/patologia , Receptores de GABA-A/análise , Receptores de N-Metil-D-Aspartato/análise , Biomarcadores/análise , Neoplasias Encefálicas/cirurgia , Calbindina 2 , Epilepsias Parciais/etiologia , Ganglioglioma/cirurgia , Glutamato Descarboxilase/análise , Hamartoma/patologia , Hamartoma/cirurgia , Humanos , Imuno-Histoquímica , Substâncias Macromoleculares , Parvalbuminas/análise , Estudos Retrospectivos , Proteína G de Ligação ao Cálcio S100/análise , Somatostatina/análise , Tirosina 3-Mono-Oxigenase/análise
4.
J Neuropathol Exp Neurol ; 52(5): 499-506, 1993 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8360703

RESUMO

The surgical treatment of chronic epilepsies is increasing rapidly. Here we report the histopathologic findings in 216 consecutive surgical specimens of patients with chronic pharmacoresistant temporal lobe epilepsy. In 75 cases (34.7%) there were tumors, all but two of which were of low histopathological grade (WHO grade I or II). The most common tumors were gangliogliomas (34 cases), pilocytic astrocytomas (17 cases), oligodendrogliomas (9 cases), fibrillary astrocytomas (6 cases), and dysembryoplastic neuroepithelial tumors (6 cases). There were 51 cases with non-neoplastic focal lesions and an additional 13 cases with tumors and non-neoplastic focal lesions within the same specimen. The most frequent non-neoplastic focal lesions were microscopic glioneuronal hamartias (32 cases), glioneuronal hamartomas (7 cases), and vascular malformations (13 cases). The hippocampal formation was structurally well preserved in 71 specimens. In 51 of these (71.8%) there was Ammon's horn sclerosis. Presurgical placement of depth electrodes was invariably associated with circumscribed defects of the brain parenchyma. The implantation of subdural electrodes was sometimes followed by chronic inflammatory changes of the leptomeninges. Our findings indicate that in the majority of patients with medically intractable temporal lobe epilepsy there are significant histopathologic findings, many of which are only rarely encountered otherwise.


Assuntos
Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/cirurgia , Adolescente , Adulto , Astrocitoma/patologia , Neoplasias Encefálicas/complicações , Criança , Epilepsia do Lobo Temporal/complicações , Feminino , Glioma/patologia , Humanos , Masculino , Neuroblastoma/patologia , Oligodendroglioma/patologia , Estudos Retrospectivos , Xantomatose/patologia
5.
J Neuropathol Exp Neurol ; 56(7): 806-10, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9210877

RESUMO

The tuberous sclerosis 2 (TSC2) gene is thought to function as a growth suppressor in sporadic and TSC-associated hamartomas and tumors. Clusters of dysplastic glial cells are a common feature of cortical tubers and subependymal nodules in tuberous sclerosis patients. In an effort to identify TSC2 gene alterations in sporadic gliomas, we detected a novel polymorphism adjacent to the 3'splice site of intron 4. We evaluated the distribution of this variant allele in a series of 244 patients with glial tumors, including 55 gangliogliomas, 31 pilocytic astrocytomas (WHO grade I), 50 astrocytomas (WHO grades II and III), and 108 glioblastomas (WHO grade IV). The allelic distribution in the general population was estimated by examining 381 healthy blood donors. This rare allele appeared in the control population and in the patients with astrocytic gliomas with a virtually identical frequency (8.14%, and 8.20%, respectively). The frequency of the rare allele in gangliogliomas, however, was significantly higher (15.5%; p = 0.024). The fact that both gangliogliomas and cortical tubers in tuberous sclerosis contain neuronal and astrocytic elements and may resemble each other histologically suggests that the TSC2 gene may be involved in the development of these tumors. The rare allele of the TSC2 gene emerges as a candidate for a predisposing factor for the formation of sporadic gangliogliomas.


Assuntos
Neoplasias Encefálicas/genética , Ganglioglioma/genética , Genes Supressores de Tumor/genética , Polimorfismo Genético/genética , Proteínas Repressoras/genética , Adulto , Alelos , Feminino , Humanos , Masculino , Splicing de RNA , Fatores de Risco , Proteína 2 do Complexo Esclerose Tuberosa , Proteínas Supressoras de Tumor
6.
J Neuropathol Exp Neurol ; 55(3): 329-41, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8786391

RESUMO

Selective neuronal vulnerability and aberrant axonal reorganization in the hippocampus may play an important role for the pathogenesis of pharmaco-resistant temporal lobe epilepsy (TLE). Interneurons containing calcium-binding proteins (CaBPs) are candidates for pathogenetically relevant neurons in the hippocampus of patients with TLE. Here we have examined the cellular localization and distribution of calretinin (CR), a recently discovered CaBP, in the hippocampus of 35 patients with TLE. There was a striking preservation of CR-immunoreactive neurons in TLE patients with Ammon's horn sclerosis (AHS). No significant differences in the distribution of CR-immunoreactive neurons were observed between patients with lesion-associated TLE and control patients without epilepsy. However, a subpopulation of CR-immunoreactive interneurons with morphological features of Cajal-Retzius-like cells, which are only transiently detectable in the normally developing hippocampus, was markedly increased in epilepsy patients with AHS. This increase did not correlate with the duration of the epileptic disorder. Another significant finding was a striking increase and reorganization of CR-immunoreactive neuropil throughout the entire molecular layer of the dentate gyrus (DG-ML) in patients with AHS as compared to patients with focal lesions and control specimens. Ultrastructural analysis identified the CR-immunoreactive axonal profiles as components of an inhibitory, intrinsic neuronal system. The presence of a CR-positive, aberrant cell population, in combination with sprouting of CR-positive axonal processes may significantly alter the gating function of the dentate gyrus and thereby increase hippocampal epileptogenicity in epilepsy patients with AHS.


Assuntos
Epilepsia do Lobo Temporal/patologia , Hipocampo/patologia , Neurônios/patologia , Proteína G de Ligação ao Cálcio S100/imunologia , Adolescente , Adulto , Idade de Início , Idoso , Calbindina 2 , Contagem de Células , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Lactente , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
7.
J Neuropathol Exp Neurol ; 59(10): 907-20, 2000 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-11079781

RESUMO

The hippocampus, amygdala complex, and entorhinal region represent anatomically linked limbic structures of the mesiotemporal lobe. Chronic seizures and mnestic deficits in patients with pharmacoresistant mesial temporal lobe epilepsy (TLE) appear to correlate with distinct patterns of histopathological alterations in these areas. The complex anatomical organization of the amygdala and entorhinal region, however, render a detailed neuropathological evaluation of surgical specimens difficult. In this study, we present a combined cytoarchitectonical, pigmentarchitectonical, myelinarchitectonical, and immunohistochemical reconstruction of the amygdala, entorhinal region, and hippocampus from surgical TLE specimens (n = 20) in order to analyze their regional and cellular patterns of pathology. Anterior mesiotemporal lobes dissected in different spatial planes were obtained from 4 autopsy control patients and used for the characterization of neuroanatomical landmarks. Lateral, basal, and granular subnuclei of the amygdala were consistently identified in the surgical specimens. Major histopathological alterations included neuronal cell loss as revealed by extracellular lipofuscin accumulation, glial satellitosis, as well as cellular and fibrillary gliosis. The regional distribution of neuropathological changes varied considerably between different subnuclei but the lateral nucleus was more often involved than basal and granular nuclei. These amygdala nuclei appeared to be more severely affected compared to the adjacent entorhinal region. In addition, patients presenting with secondary generalized tonic-clonic seizures showed significantly more damage in mesiotemporal structures. Pathological alterations in the amygdala and entorhinal region were found to be associated with Ammon's horn sclerosis in most but not all cases. Our findings reveal the amygdala as a major target for epilepsy-associated neuronal cell damage. Significant variations in the lesional pattern among patients with chronic TLE would also be compatible with different spreading pathways of epileptogenic activity within the mesial temporal lobe.


Assuntos
Tonsila do Cerebelo/patologia , Córtex Entorrinal/patologia , Epilepsia do Lobo Temporal/patologia , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Pré-Escolar , Resistência a Medicamentos , Epilepsia do Lobo Temporal/tratamento farmacológico , Epilepsia do Lobo Temporal/cirurgia , Feminino , Gliose/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose , Lobo Temporal/patologia
8.
Brain Pathol ; 3(4): 371-80, 1993 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8293193

RESUMO

The surgical treatment of chronic epilepsies is increasing rapidly and involves neuropathologists in the care of patients with chronic and medically intractable seizure disorders. Herein we review the histopathologic findings in 279 consecutive surgical specimens of patients with chronic pharmacoresistant epileptic disorders. Aspects that are relevant to the diagnostic surgical pathologist such as the terminology of developmental lesions and Ammon's horn sclerosis are discussed. In 87 cases (31.2%), there were tumors in which all but two were of low histopathological grade (WHO grade I or grade II). The most common tumors were gangliogliomas, pilocytic astrocytomas, oligodendrogliomas, fibrillary astrocytomas and dysembryoplastic neuroepithelial tumors. Among the most frequent non-neoplastic focal lesions, microscopic glioneuronal hamartias, circumscribed vascular malformations, glioneuronal hamartomas and porencephalic defects were most frequent. The hippocampal formation was structurally well preserved in 71 specimens of patients with temporal lobe epilepsy. In 51 of these (71.8%) cases, Ammon's horn sclerosis was present. The findings suggest that the structural lesions observed in the great majority of the specimens are closely related to the pathogenesis of intractable seizures.


Assuntos
Encéfalo/patologia , Encéfalo/cirurgia , Epilepsia/patologia , Epilepsia/cirurgia , Doença Crônica , Humanos
9.
Eur J Cancer ; 36(5): 610-4, 2000 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10738125

RESUMO

The aim of this study was to determine whether p53 is helpful in making the decision to undergo cystectomy in T1, G3 transitional cell carcinoma (TCC) of the bladder, by prospectively comparing the p53 status of bladder biopsies with the histology and p53 status of the corresponding cystectomy specimens. From January 1996 to August 1997, 38 consecutive patients with T1G3 TCC at 6 different centres were enrolled into the study. Bladder biopsies and cystectomy specimens were examined with three different antibodies against p53. The p53 status of each bladder biopsy was compared with p53 status, tumour stage and grade of the cystectomy specimen. An independent evaluation of the histology and immunohistochemistry was carried out by two pathologists. 15 of 38 patients (39%) were found to have a higher tumour stage in the cystectomy specimen compared with the staging by transurethral resection of the bladder tumour (TUR-B). 3 patients did not show residual tumour in the cystectomy specimen. No differences in p53 positivity were noted between the different antibodies. 14 of 31 evaluable tumours (45%) were p53 positive at the time of the TUR-B. p53 staining of the TUR-B specimen did not correctly predict the residual tumour in the cystectomy specimen. We, therefore, concluded that compared with standard histopathology, the p53 status of the TUR-B specimen does not provide additional relevant information with regard to local tumour staging and, thus, is not helpful in making the decision for or against a cystectomy.


Assuntos
Carcinoma de Células de Transição/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Adulto , Idoso , Biópsia , Carcinoma de Células de Transição/patologia , Carcinoma de Células de Transição/cirurgia , Cistectomia/métodos , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Estudos Prospectivos , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
10.
Am J Surg Pathol ; 14(6): 590-5, 1990 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-2186646

RESUMO

Numerous microscopic foci of exocrine pancreatic tissue consisting of acini and small ductules were distributed throughout the liver of a 41-year-old patient with severe posthepatitic cirrhosis. The acinar cells were characterized by abundant zymogen granules on electron microscopic examination and a strong reaction with antibodies to alpha-amylase on immunoperoxidase staining. The pancreatic tissue was associated with proliferations of bile ductules within areas of fibrosis. No relationship with hepatocytes was observed. A metaplastic origin of the pancreatic tissue from the intrahepatic biliary epithelium is suggested.


Assuntos
Coristoma/patologia , Neoplasias Hepáticas/patologia , Pâncreas , Adulto , Coristoma/ultraestrutura , Feminino , Humanos , Técnicas Imunoenzimáticas , Neoplasias Hepáticas/ultraestrutura , Metaplasia/patologia , Microscopia Eletrônica , Pâncreas/patologia , Pâncreas/ultraestrutura
11.
Am J Surg Pathol ; 14(2): 188-93, 1990 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2154142

RESUMO

We present an unusual case of multicentric malignant fibrous histiocytoma of soft tissue. Over the past 24 years, a 67-year-old woman developed malignant fibrous histiocytoma in four different soft-tissue sites. There were two local recurrences of one of the tumors. Currently, there is no evidence of visceral involvement. The evidence suggests that this patient has a predisposition of the connective tissue to develop malignant tumors of fibrohistiocytic differentiation.


Assuntos
Histiocitoma Fibroso Benigno/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias de Tecidos Moles/patologia , Idoso , Feminino , Humanos
12.
J Histochem Cytochem ; 40(9): 1269-73, 1992 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-1354677

RESUMO

We describe the effects of tissue preservation, fixation time, and hydrolytic treatment on the detection of proliferating cell nuclear antigen (PCNA) by immunoperoxidase staining with three commercial anti-PCNA antibodies (19A2, 19F4, PC10). Our goal was to provide guidelines for PCNA immunohistochemistry in formalin-fixed, paraffin-embedded specimens. In proliferative cell compartments, nuclear staining was achieved with all three antibodies. In some cases PCNA was also expressed in non-proliferative, histologically normal tissues associated with tumors or other lesions elsewhere. In most autopsy specimens PNCA immunoreactivity was markedly diminished as compared with similar surgical specimens. Incubation overnight with primary antibody at 4 degrees C enhanced PCNA immunoreactivity over incubation at 42 degrees C for 45 min. Pre-treatment with 2 N HCl did not increase staining. Staining with the PC10 antibody was much better preserved than staining with the antibodies 19A2 and 19F4 after prolonged formalin fixation of surgical specimens and in tissues obtained at autopsy. With all three antibodies, however, PCNA immunoreactivity was well preserved during formalin fixation for 8-24 hr and during fixation delays for 8 hr at room temperature. This indicates that PCNA is stable under conditions routinely encountered in diagnostic surgical pathology and facilitates its potential use as a diagnostic proliferation marker.


Assuntos
Autoantígenos/análise , Técnicas Imunoenzimáticas , Proteínas Nucleares/análise , Humanos , Concentração de Íons de Hidrogênio , Hidrólise , Patologia Cirúrgica , Antígeno Nuclear de Célula em Proliferação , Fixação de Tecidos
13.
J Histochem Cytochem ; 44(10): 1167-71, 1996 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-8813082

RESUMO

The monoclonal antibody A60 specifically recognizes the DNA-binding, neuron-specific protein NeuN, which is present in most neuronal cell types of vertebrates. In this study we demonstrate the potential use of NeuN as a diagnostic neuronal marker using a wide range of formalin-fixed, paraffin-embedded human surgical and autopsy specimens from the central and peripheral nervous system. After microwave antigen retrieval, almost all neuronal populations revealed strong immunoreactivity for NeuN in nuclei, perikarya, and some proximal neuronal processes, whereas more distal axon cylinders and dendritic ramifications were not stained. The stain greatly enhanced the gray matter architecture. NeuN immunoreactivity was not detected in Purkinje cells, most neurons of the internal nuclear layer of the retina, and in sympathetic chain ganglia. We examined nine gangliogliomas and 14 dysembryoplastic neuroepithelial tumors, one ganglioneuroma, and one dysplastic cerebellar gangliocytoma. The neuronal component of all of these lesions showed marked immunoreactivity for NeuN. In addition, NeuN immunoreactivity was focally seen in one of seven medulloblastomas with prominent neuronal differentiation. There was no staining of non-neuronal structures. The results indicate that NeuN immunoreactivity is a sensitive and specific neuronal marker in formalin-fixed, paraffin-embedded tissues, and may be useful in diagnostic histopathology.


Assuntos
Biomarcadores Tumorais/análise , Técnicas Imunoenzimáticas , Proteínas de Neoplasias/análise , Neoplasias de Tecido Nervoso/química , Proteínas do Tecido Nervoso/análise , Neurônios/química , Animais , Anticorpos Monoclonais/imunologia , Biomarcadores/análise , Carcinoma/química , Carcinoma/diagnóstico , Carcinoma/ultraestrutura , Sistema Nervoso Central/química , Sistema Nervoso Central/ultraestrutura , Diagnóstico Diferencial , Formaldeído , Gânglios/química , Gânglios/ultraestrutura , Hamartoma/química , Hamartoma/diagnóstico , Hamartoma/ultraestrutura , Humanos , Meduloblastoma/química , Meduloblastoma/diagnóstico , Meduloblastoma/ultraestrutura , Camundongos , Neoplasias de Tecido Nervoso/diagnóstico , Neoplasias de Tecido Nervoso/patologia , Neoplasias Neuroepiteliomatosas/química , Neoplasias Neuroepiteliomatosas/diagnóstico , Neoplasias Neuroepiteliomatosas/ultraestrutura , Neurônios/ultraestrutura , Inclusão em Parafina , Nervos Periféricos/química , Nervos Periféricos/ultraestrutura , Células de Purkinje/química , Sensibilidade e Especificidade , Fixação de Tecidos
14.
Am J Cardiol ; 62(1): 59-66, 1988 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-2968043

RESUMO

The prognostic value of a left ventricular (LV) mass index (g/m2) estimated from an electrocardiographic model and radiographic estimates of the relative heart volume (ml/m2) and cardiothoracic ratio for predicting the risk of cardiovascular disease mortality were investigated using Cox regression analysis to adjust for age, systolic blood pressure and history of heart attack in 1,807 men (1,609 white, 198 black) and 2,143 women (1,884 white, 259 black). The study population (ages 35 to 74 years at baseline) was followed from 5 to 12 years (average 9.5 years) for cardiovascular disease mortality. LV mass index and relative heart volume were independent predictors of cardiovascular disease mortality among white men. All 3 cardiac size estimates were independent predictors for cardiovascular disease mortality among white and black women. When LV mass index was used as a dichotomized variable to indicate the presence or absence of LV hypertrophy, the age-adjusted relative risk of cardiovascular disease mortality was 2.48 (95% confidence interval 1.77 to 3.46) for white men, 3.03 (1.49 to 6.16) for black men, 1.86 (1.21 to 2.87) for white women and 2.05 (0.83 to 5.05) for black women. The corresponding prevalence of LV hypertrophy was 15.4% for white men, 36.6% for black men, 20.1% for white women and 17.4% for black women. It is concluded that the electrocardiographic estimate of LV mass index can identify a substantially larger fraction of persons at increased risk for cardiovascular mortality than conventional electrocardiographic criteria for LV hypertrophy and that LV mass index estimated by electrocardiogram is a valuable supplement to radiographic cardiac size estimates in epidemiologic applications.


Assuntos
Volume Cardíaco , Doenças Cardiovasculares/mortalidade , Eletrocardiografia , Coração/diagnóstico por imagem , Adulto , Idoso , População Negra , Pressão Sanguínea , Cardiomegalia/patologia , Doenças Cardiovasculares/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Radiografia , Fatores de Risco , Fatores Sexuais , Estados Unidos
15.
Am J Med Genet ; 67(2): 229-31, 1996 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-8723054

RESUMO

The term genomic imprinting has been used to refer to the differential expression of genetic material depending on whether it has come from the male or female parent. In humans, the chromosomal region 11p15.5 has been shown to contain 2 imprinted genes (H19 and IGF2). The gene for the dopamine D4 receptor (DRD4), which is of great interest for research into neuropsychiatric disorders and psychopharmacology, is also located in this area. In the present study, we have examined the imprinting status of the DRD4 gene in brain tissue of an epileptic patient who was heterozygous for a 12 bp repeat polymorphism in exon 1 of the DRD4 gene. We show that both alleles are expressed in equivalent amounts. We therefore conclude that the DRD4 gene is not imprinted in the human brain.


Assuntos
Impressão Genômica , Receptores de Dopamina D2/genética , Sequência de Bases , Cromossomos Humanos Par 11 , Primers do DNA , Feminino , Humanos , Masculino , Dados de Sequência Molecular , Receptores de Dopamina D4
16.
J Clin Epidemiol ; 50(7): 787-91, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9253389

RESUMO

Mortality from myocardial infarction (MI) has declined in many countries and the reasons for the decline have not been fully quantified. We used the database of the Halifax County MONICA Project to test the hypothesis that the decline of in-hospital mortality from MI can be explained by a trend toward less severe disease as opposed to improved treatment. During the study period 1984-1993, 14,130 people aged 25-74 had been admitted to hospital with suspected MI. Of these, 3774 were diagnosed as definite MI by standardized criteria (480 fatal). For each patient, clinical history, serial cardiac enzymes, and ECG treatment regimen during hospital stay were extracted from patient charts. Survival status 28 days after onset of symptoms was determined. A severity index predicting 28-day case fatality was derived from health status at admission time. During the study period the rate of definite MI in the MONICA target population showed a general downward trend from 221 to 179 per 100,000/year (p = 0.0002). The severity index increased during the observation time (p < 0.0001), predicting 25% higher mortality. Case fatality fluctuated, but showed a marginally significant decline. We conclude that part of the decreased in-hospital mortality from MI is due to lower attack rates. The remainder occurred despite increased case severity and is possibly due to improved in-hospital treatment.


Assuntos
Mortalidade Hospitalar/tendências , Infarto do Miocárdio/mortalidade , Adulto , Idoso , Doença das Coronárias/epidemiologia , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/classificação , Infarto do Miocárdio/epidemiologia , Nova Escócia/epidemiologia , Prevalência , Fatores de Risco , Índice de Gravidade de Doença
17.
Int J Epidemiol ; 25(4): 763-9, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8921454

RESUMO

BACKGROUND: The study was set up to assess the effect of recruitment methods on participation rate, response bias and cardiovascular risk factor estimates. METHODS: Two random samples of men and women in Halifax County aged 25-74 were drawn from the same sampling frame. Their respective sizes were 1007 (NSHHS) and 3036 (MONICA) people. Recruitment by Nova Scotia Heart Health Survey (NSHHS) was through face-to-face contact, whereas the MONICA survey relied on invitation by mail. Outcome measures were response rates at various stages of the recruitment process and the differences in cardiovascular risk factor estimates. RESULTS: Face-to-face recruitment located 51% and mail recruitment located 47% of their respective samples; face-to-face recruitment resulted in fewer individuals who refused to participate in the survey, but also produced fewer who were prepared to provide blood samples in addition to answering questionnaires. By-mail recruits were more likely to have post-secondary education, but did not differ in the proportion of smokers, mean diastolic blood pressure or body mass index, if controlled for education level, gender and age. However, the mean systolic blood pressure was 5.7 mmHg higher and the mean cholesterol level 0.44 mmol/l lower in face-to-face recruits. CONCLUSIONS: Controlling for age, gender and education level eliminates the effect of recruitment bias on most cardiovascular risk factors estimates. The exceptions in our study were systolic blood pressure and cholesterol, where methodological factors may have played a role.


Assuntos
Doenças Cardiovasculares/epidemiologia , Fatores Epidemiológicos , Inquéritos Epidemiológicos , Projetos de Pesquisa , Adulto , Idoso , Análise de Variância , Viés , Doenças Cardiovasculares/prevenção & controle , Coleta de Dados/métodos , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Nova Escócia/epidemiologia , Fatores de Risco
18.
Am J Hypertens ; 8(4 Pt 1): 422-5, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7619357

RESUMO

The present study evaluated the relationship of plasma norepinephrine (NE) and aortic distensibility (AOD) in a group of elderly patients with isolated systolic hypertension. Aortic distensibility was calculated as AOD = 2 x (delta aortic diameter)/diastolic aortic diameter) x (delta aortic pressure). Results indicate that the aortic diameters were significantly increased while the diastolic blood pressure and heart rate were decreased, in response to combined alpha- and beta-receptor blockade (labetalol). However, we found that AOD was not significantly related to plasma NE. We therefore conclude that AOD can be increased in elderly hypertensives by alpha-beta-blockade, as has been found in younger patients, but plasma NE is not a useful marker for AOD in this population.


Assuntos
Aorta/diagnóstico por imagem , Hipertensão/sangue , Hipertensão/diagnóstico por imagem , Norepinefrina/sangue , Idoso , Idoso de 80 Anos ou mais , Aorta/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Ecocardiografia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipertensão/tratamento farmacológico , Labetalol/uso terapêutico , Masculino , Pessoa de Meia-Idade
19.
Virchows Arch ; 438(2): 116-20, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11253112

RESUMO

Thrombospondin-1 (TSP-1) is a multifunctional platelet and extracellular matrix protein that is involved in angiogenesis. Under certain pathological conditions, e.g., malignant tumors, high concentrations of TSP-1 work as an angiogenic agonist. Here we examined 98 pancreatic carcinomas with respect to TSP-1 immunoreactivity and its correlation to intratumoral microvessel density (MVD), a representation of the overall degree of angiogenesis in carcinomas. Northern blot analysis for TSP-1 mRNA was performed in seven additional cases. Eighty-seven tumors showed strong TSP-1 immunoreactivity, nine carcinomas were only weakly positive, and two lesions were negative for TSP-1. TSP-1 immunoreactivity was detected in the extracellular matrix, mostly at the invasion front of the tumor. Using Northern blot analysis, we observed high levels of TSP-1 mRNA in three out of seven pancreatic carcinomas. The mean MVD in pancreatic carcinoma was 38.8 vessels per mm2. Tumors with a high expression of TSP-1 showed a higher MVD and the correlation between TSP-1 immunoreactivity and microvessel density was highly significant (P=0.003). As a modulator of angiogenesis, TSP-1 is strongly expressed in most pancreatic adenocarcinomas and is likely to contribute to the extensive neovascularization and spread of this highly aggressive tumor.


Assuntos
Adenocarcinoma/irrigação sanguínea , Neovascularização Patológica/metabolismo , Neoplasias Pancreáticas/irrigação sanguínea , Trombospondina 1/metabolismo , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Northern Blotting , Feminino , Expressão Gênica , Humanos , Imuno-Histoquímica , Masculino , Microcirculação , Pessoa de Meia-Idade , Neovascularização Patológica/patologia , Neoplasias Pancreáticas/patologia , RNA Mensageiro/metabolismo , Trombospondina 1/genética
20.
Microsc Res Tech ; 46(1): 53-8, 1999 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-10402272

RESUMO

The etiology and pathogenesis of epilepsy-associated local lesions remain largely unknown. Histopathologically, the most frequent lesions comprise gangliogliomas and glioneuronal malformations, i.e., hamartias or hamartomas, with a preferred location in the temporal lobe of young patients. A characteristic histopathological admixture of glial and neuronal elements, the focal appearance and the benign clinical behaviour suggest a malformative nature. So far, no molecular genetic alterations specifically involved in the pathogenesis of these glioneuronal lesions have been identified. However, immunohistochemical analysis revealed distinct distribution patterns of oncofetal antigens. The embryonic form of the neural cell adhesion molecule is present within glioneuronal hamartias, indicating an early migrational disorder. Recently, we have observed immunoreactivity for the stem cell marker CD34 in the majority of gangliogliomas and glioneuronal hamartomas. Based on these findings, we propose a common origin of gangliogliomas and glioneuronal hamartomas from a bipotent precursor that undergoes abnormal glioneuronal development.


Assuntos
Neoplasias Encefálicas/patologia , Epilepsia/patologia , Ganglioglioma/patologia , Lobo Temporal/patologia , Antígenos CD34/análise , Antígenos de Neoplasias/análise , Biomarcadores/análise , Neoplasias Encefálicas/química , Neoplasias Encefálicas/etiologia , Epilepsia/complicações , Ganglioglioma/química , Ganglioglioma/etiologia , Hamartoma/química , Hamartoma/etiologia , Hamartoma/patologia , Histocitoquímica/métodos , Humanos
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